EMBO Molecular Medicine (Dec 2018)
CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline
- Marc Suárez‐Calvet,
- Anja Capell,
- Miguel Ángel Araque Caballero,
- Estrella Morenas‐Rodríguez,
- Katrin Fellerer,
- Nicolai Franzmeier,
- Gernot Kleinberger,
- Erden Eren,
- Yuetiva Deming,
- Laura Piccio,
- Celeste M Karch,
- Carlos Cruchaga,
- Katrina Paumier,
- Randall J Bateman,
- Anne M Fagan,
- John C Morris,
- Johannes Levin,
- Adrian Danek,
- Mathias Jucker,
- Colin L Masters,
- Martin N Rossor,
- John M Ringman,
- Leslie M Shaw,
- John Q Trojanowski,
- Michael Weiner,
- Michael Ewers,
- Christian Haass,
- the Dominantly Inherited Alzheimer Network,
- the Alzheimer's Disease Neuroimaging Initiative
Affiliations
- Marc Suárez‐Calvet
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Anja Capell
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Miguel Ángel Araque Caballero
- Institute for Stroke and Dementia Research Klinikum der Universität München Ludwig‐Maximilians‐Universität München Munich Germany
- Estrella Morenas‐Rodríguez
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Katrin Fellerer
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Nicolai Franzmeier
- Institute for Stroke and Dementia Research Klinikum der Universität München Ludwig‐Maximilians‐Universität München Munich Germany
- Gernot Kleinberger
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Erden Eren
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- Yuetiva Deming
- Department of Psychiatry Washington University School of Medicine St. Louis MO USA
- Laura Piccio
- Department of Neurology Washington University School of Medicine St. Louis MO USA
- Celeste M Karch
- Department of Psychiatry Washington University School of Medicine St. Louis MO USA
- Carlos Cruchaga
- Department of Psychiatry Washington University School of Medicine St. Louis MO USA
- Katrina Paumier
- Department of Neurology Washington University School of Medicine St. Louis MO USA
- Randall J Bateman
- Department of Neurology Washington University School of Medicine St. Louis MO USA
- Anne M Fagan
- Department of Neurology Washington University School of Medicine St. Louis MO USA
- John C Morris
- Department of Neurology Washington University School of Medicine St. Louis MO USA
- Johannes Levin
- German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany
- Adrian Danek
- Department of Neurology Ludwig‐Maximilians‐Universität München Munich Germany
- Mathias Jucker
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Tübingen Germany
- Colin L Masters
- The Florey Institute of Neuroscience and Mental Health University of Melbourne Parkville Vic. Australia
- Martin N Rossor
- Dementia Research Centre UCL Institute of Neurology London UK
- John M Ringman
- Department of Neurology Keck School of Medicine University of Southern California Los Angeles CA USA
- Leslie M Shaw
- Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA
- John Q Trojanowski
- Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA
- Michael Weiner
- University of California at San Francisco San Francisco CA USA
- Michael Ewers
- Institute for Stroke and Dementia Research Klinikum der Universität München Ludwig‐Maximilians‐Universität München Munich Germany
- Christian Haass
- Chair of Metabolic Biochemistry Biomedical Center (BMC) Faculty of Medicine Ludwig‐Maximilians‐Universität München Munich Germany
- the Dominantly Inherited Alzheimer Network
- the Alzheimer's Disease Neuroimaging Initiative
- DOI
- https://doi.org/10.15252/emmm.201809712
- Journal volume & issue
-
Vol. 10,
no. 12
pp. n/a – n/a
Abstract
Abstract Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.
Keywords
